Osteonecrosis of the jaw, atypical fractures and other less frequent adverse events associated with bisphosphonates
Authors:
J. Treglerová 1; J. Zelinka 1; Z. Adam 2; L. Pour 2; M. Krejčí 2; L. Ostřížková 2; V. Sandecká 2; M. Štork 2; Z. Král 2; A. Čermák 3
Authors‘ workplace:
Interní hematologická a onkologická klinika LF MU a FN Brno
1; Klinika ústní, čelistní a obličejové chirurgie FN Brno a LF MU
2; Urologická klinika LF MU a FN Brno
3
Published in:
Transfuze Hematol. dnes,25, 2019, No. 3, p. 242-251.
Category:
Review/Educational Papers
Overview
Bisphosphonates have been an integral part of the complex treatment of multiple myeloma for more than three decades. They slow down osteolysis and thus help improve quality of life. However, their long-term administration is associated with two serious, usually late onset complications, namely medication related osteonecrosis of the jaw, which occurs in 6–9% of patients and more rarely, atypical fractures. Healing of both these complications is very protracted, which is why emphasis must be placed on their prevention, on discussing the risks with patients and also on a detailed dental exam before starting treatment and during its course. An effort should also be made to limit the administration of these agents to the shortest necessary period of time. However, osteonecrosis of the jaw does not develop only as a consequence of bisphosphonate treatment. Some new agents (denosumab and others) used in the treatment of oncological patients also cause this complication. This article presents an overview of drugs used in oncology today and which increase the risk of osteonecrosis of the jaw. Rarer complications of long-term bisphosphonate treatment also include atypical fractures. The aim of this article is to inform about the risks associated with long-term bisphosphonate treatment, which must be taken into consideration when making decisions about starting treatment and its duration.
Keywords:
bisphosphonates – medication related osteonecrosis of the jaw – atypical fractures
Sources
1. Russell RG. Bisphosphonates: the first 40 years. Bone 2011; 49(1): 2–19.
2. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003; 61(9): 1115–1117.
3. Ruggiero SL, Mehrota B. Osteonecrosis of the jaws associated with the use of bisphophonates; a review of 63 cases. J Oral Maxillofac Surg 2004; 62:527–534.
4. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonates--induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment. J Oral Maxillofac Surg 2005; 63:1567–1575.
5. Ferlito S, Liardo C, Puzzo S. Bisphosponates and dental implants: a case report and a brief review of literature. Minerva Stomatol 2011; 60(1–2): 75–81.
6. Montoya-Carralero JM, Parra-Mino P, Ramírez-Fernández P, et al. Dental implants in patients treated with oral bisphosphonates: a bibliographic review. Med Oral Patol Oral Cir Bucal 2010; 15(1): e65–e69.
7. Favia G, Piattelli A, Sportelli P, Capodiferro S, Iezzi G. Osteonecrosis of the posterior mandible after implant insertion: a clinical and histological case report. Clin Implant Dent Relat Res 2011; 13(1): 58–63.
8. Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med 2008; 358(12): 1304–1306.
9. Tonogai I, Goto T, Hamada D, Iwame T, et al. Bilateral atypical femoral fractures in a patient with multiple myeloma treated with intravenous bisphosphonate therapy. Case Rep Orthop 2014; 2014: 452418. doi: 10.1155/2014/452418.
10. Puhaindran ME, Farooki A, Steensma MR, et al. Atypical subtrochanteric femoral fractures in patients with skeletal malignant involvement treated with intravenous bisphosphonates. J Bone Joint Surg Am 2011; 93(13): 1235–1242.
11. Epperla N, Pathak R. Hypocalcemia secondary to zoledronate therapy in a patient with low vitamin D level. WMJ 2015; 114(4): 163–166.
12. Noriega Aldave AP, Jaiswal S. Severe resistant hypocalcemia in multiple myeloma after zoledronic acid administration: a case report. J Med Case Rep 2014; 8: 353.
13. Kreutle V, Blum C, Meier C, et al. Bisphosphonate induced hypocalcaemia – report of six cases and review of the literature. Swiss Med Wkly 2014; 144: w13979.
14. Do WS, Park JK, Park MI, et al. Bisphosphonate-induced severe hypocalcemia – a case report. J Bone Metab 2012; 19(2): 139–145.
15. Atula S, Powles T, Paterson A, McCloskey E: Extended safety profile of oral clodronate after long-term use in primary breast cancer patients. Drugs Safety 2003; 26: 661–671.
16. Markowitz GS, Appel GB, Fine PL, et al. Collapsing focal segmental glomerulosclerosis wollowing treatment with high dose pamidronate J Am Soc Nephrol 2001; 12: 1164–1172
17. Markowitz GS, Fine, PL, Stack FJ, et al. Toxic acute tubular necrosis following treatment with zolendronate (Zometa). Kidney Int 2003; 64: 281–289.
18. Sauter M, Jülg B, Porubsky S, et al. Nephrotic-range proteinuria following pamidronate therapy in a patient with metastatic breast cancer: Mitochondrial toxicity as a pathogenetic koncept? Amer J Kidney Dis 2006; 47: 1075–1080.
19. Ruggiero SL, Dodson TB Fantasia J, et al. American Association of Oral and Maxillofacial Surgeons position paper on medication releated ostenecrosis of the jaw 2014 update. J Oral Maxillofac Surg 2014; 72: 1938–1956.
20. Rosella D, Papi P, Giardino R. Medication-related osteonecrosis of the jaw: clinical and practical guidelines. J Int Soc Prev Community Dent 2016; 6(2): 97–104.
21. Fusco V, Santini D, Armento G, et al. Osteonecrosis of jaw beyond antiresorptive (bone-targeted) agents: new horizons in oncology. Expert Opin Drug Saf 2016; 15(7): 925–935.
22. Qi WX, Tang LN, He AN, et al. Risk of osteonecrosis of the jaw in cancer patients receiving denosumab: a meta-analysis of seven randomized controlled trials. Int J Clin Oncol 2014; 19: 403–408.
23. Estilo CL, Fornier M, Farooki A, et al. Osteonecrosis of the jaw related to bevacizumab. J Clin Oncol 2008; 26(24): 4037–4038.
24. Greuter S, Schmid F, Ruhstaller T, et al. Bevacizumab-associated osteonecrosis of the jaw. Ann Oncol 2008; 19(12): 2091–2092.
25. Brunello A, Saia G, Bedogni A, et al Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma. Bone 2009; 44(1): 173–175.
26. Koch FP, Walter C, Hansen T, et al. Osteonecrosis of the jaw related to sunitinib. Oral Maxillofac Surg 2011; 15(1): 63–66.
27. Fusco V, Porta C, Saia G, et al. Osteonecrosis of the jaw in patients with metastatic renal cell cancer treated with bisphosphonates and targeted agents: results of an Italian multicenter study and review of the literature. Clin Genitourin Cancer 2015; 13(4): 287–294.
28. Mawardi H, Enzinger P, McCleary N, et al. Osteonecrosis of the jaw associated with ziv-aflibercept. J Gastrointest Oncol 2016; 7(6): E81–E87.
29. Marino R, Orlandi F, Arecco F, et al. Osteonecrosis of the jaw in a patient receiving cabozantinib. Aust Dent J 2015; 60(4): 528–531.
30. Garuti F, Camelli V, Spinardi L, Bucci L, Trevisani F. Osteonecrosis of the jaw during sorafenib therapy for hepatocellular carcinoma. Tumori 2016; 102(Suppl 2): S69–S70.
31. Giancola F, Campisi G, Lo Russo L, et al. Osteonecrosis of the jaw related to everolimus and bisphosphonate: a unique case report? Ann Stomatol (Roma) 2013; 4(Suppl 2): 20–21.
32. Kim DW, Jung YS, Park HS, et al. Osteonecrosis of the jaw related to everolimus: a case report. Br J Oral Maxillofac Surg 2013; 51(8): e302–e304.
33. Durie BG, Katz, M, Crowley J. Osteonecrosis of the jaw and bisphosphonate. N Engl J Med 2005; 353: 99–102.
34. Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005; 23: 8580–8587.
35. Bedogni A, Fusco V, Agrillo A, Campisi G. Learning from experience. Proposal of a refined definition and staging system for bisphosphonate-related osteonecrosis of the jaw (BRONJ) Oral Dis 2012; 18: 621–623.
36. Fedele S, Bedogni G, Scoletta M, et al. Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed. Br J Oral Maxillofac Surg 2015; 53(1): 13–17.
37. Marx RE. Oral & intravenous bisphosphonate-induced osteonecrosis of the jaws: history, etiology, prevention, and treatment. 1st Ed. New Malden, Quintessence Publishing, 2007;1–160.
38. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws – 2009 update. J Oral Maxillofac Surg 2009; 67(5 Suppl): 2–12.
39. Damm DD, Jones DM. Bisphosphonate-related osteonecrosis of the jaws: A potential alternative to drug holidays. Gen Dent 2013; 61: 33–38.
40. Hellstein JW, Adler RA, Edwards B, et al. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 2011; 142: 1243–1251.
41. Walter C, Al-Nawas B, Wolff T, Schiegnitz E, Grötz KA. Dental implants in patients treated with antiresorptive medication - a systematic literature review. Int J Implant Dent 2016; 2(1): 9.
42. de-Freitas NR, Lima LB, de-Moura MB, et al. Bisphosphonate treatment and dental implants: A systematic review. Med Oral Patol Oral Cir Bucal 2016; 21(5): e644–e651.
43. Rugani P, Acham S, Kirnbauer B, Truschnegg A, Obermayer-Pietsch B, Jakse N. Stage-related treatment concept of medication-related osteonecrosis of the jaw-a case series. Clin Oral Investig 2015; 19: 1329–1338.
44. Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab 2008; 93(8): 2948–2952.
45. Kwek EB, Koh JS, Howe TS. More on atypical fractures of the femoral diaphysis. N Engl J Med 2008; 359(3): 316–317.
46. Lee P, Seibel MJ. More on atypical fractures of the femoral diaphysis. N Engl J Med 2008; 359(3): 317–318.
47. Whyte MP. Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. J Bone Miner Res 2009; 24(6): 1132–1134.
48. Black DM, Kelly MP, Genant HK, et al. Fracture Intervention Trial Steering Committee; HORIZON Pivotal Fracture Trial Steering Committee. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 2010; 362(19): 1761–1771.
49. Breglia MD, Carter JD. Atypical insufficiency fracture of the tibia-associated with long-term bisphosphonate therapy. J Clin Rheumatol 2010; 16(2): 76–78.
50. Schneider JP. Should bisphosphonates continued indefinitely. An unusual fracture in healthy woman ond long-term bisphosphonate. Geriatrics 2006; 61: 31–33.
51. Wernecke G, Namduri S, DiCarlo EF, et al. Case report of spontaneous nonspinal fracture in multiple myeloma pacient on long term pamidronate and zoledronic acid. HSS J 2008; 4: 123–127
52. Grasko JM, Hermann RP, Vasikaran SD. Recurrent low-energy femoral shift fratures and osteonecrosis of the jaw in a case of multiple myeloma treated with bisphosphonates. J Oral Maxillofac Surg 2009; 67: 645–649.
53. Waterman GN, Yellin O, Jamshidinia K, et al. Metatarsal stress fractures in patients with multiple myeloma treated with long-term bisphosphonates: a report of six cases. J Bone Joint Surg Am 2011; 93(18): e106. doi: 10.2106/JBJS.J.00455.
54. Adam Z, Sprláková-Puková A, Chaloupka R. et al. Atypická fraktura metatarsální kostni u pacienta s mnohočetným myelomem, který byl dlouhodobě léčeb bisfosfonáty. Vnitr Lek 2013; 59(11): 1022–1026.
55. Adam Z, Kozumpliková M, Pour L, et al. Osteonekróza čelisti v průběhu podávání léčby mnohočetného myelomu bisfosfonáty. Vnitř Lék 2006; 52(2): 176–180.
56. Maisnar V, Pour L, Krejčí M, et al. Doporučení vypracované Českou myelomovou skupinou, Myelomovou sekcí České hematologické společnosti a Slovenskou Myelómovou Spoločností pro diagnostiku a léčbu mnohočetného myelomuu mnohočetného myelomu. Transfuze Hematol dnes 2018; 24(Supl 1): 1–157.
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Haematology Internal medicine Clinical oncologyArticle was published in
Transfusion and Haematology Today
2019 Issue 3
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